Ryanodine receptor dysfunction in human disorders

Regulation of intracellular calcium (Ca2+) is critical in all cell types. The ryanodine receptor (RyR), an intracellular Ca2+ release channel located on the sarco/endoplasmic reticulum (SR/ER), releases Ca2+ from intracellular stores to activate critical functions including muscle contraction and neurotransmitter release. Dysfunctional RyR-mediated Ca2+ handling has been implicated in the pathogenesis of inherited and non-inherited conditions including heart failure, cardiac arrhythmias, skeletal myopathies, diabetes, and neurode-generative diseases. Here we have reviewed the evidence linking human disorders to RyR dysfunction and describe novel approaches to RyR-targeted therapeutics.